Abstract 3827: Predictions for recurrence of non-muscle invasive bladder cancers by circulating miRNAs

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Circulating microRNAs (miRNAs) have been extensively associated with disease conditions, and shown to be involved in tumorigenesis. In the current study, we aimed to identify miRNAs which are present specifically in the serum of non-muscle invasive bladder cancer (NMIBC) patients and correlate these miRNAs with clinical outcomes. Method: A pilot study was first conducted to profile the expression of 754 miRNAs using the Taqman® microRNA Array and identified 89 miRNAs that can be detected at high levels in more than 30% of samples. In this study, we applied a two-stage design with discovery phase of 280 cases followed by the validation phase of 276 cases using the Fluidigm BioMark™ System to assess whether these 89 miRNAs were associated with bladder cancer clinical outcomes. Results: Among 280 cases in the discovery phase, 134 recurrence events were observed. Further stratification by treatment showed that 147 patients received Bacillus Calmette-Guerin (BCG) treatment and 78 patients received transurethethral resection only (TUR). COX regression on dichotomized expression of miRNAs revealed that 2 and 6 miRNAs were associated with recurrence in the BCG group and the TUR group with p-values <0.05, respectively. The most significant observed association with recurrence had p-values of 0.008(BCG) and 0.005 (TUR). We constructed risk scores for recurrence using previous miRNAs identified by COX regression. Patients with high risk scores had significantly shorter recurrence-free survival in BCG group (p=0.006, mean survival time 9.04 and undefined for high risk and low risk scores) but not in TUR group possibly due to small sample size (p=0.114, mean survival time 4.60 and 14.04). We are in the progress of further verifying associations between candidate miRNAs and clinical outcomes in an additional 276 NIMBC samples. Conclusion: Our preliminary results demonstrate the potential of miRNAs as predictive markers for NMIBC recurrence. Citation Format: Shu-Hong Lin, Jie Lian, Yuanqing Ye, Colin P. Dinney, Xifeng Wu. Predictions for recurrence of non-muscle invasive bladder cancers by circulating miRNAs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3827. doi:10.1158/1538-7445.AM2014-3827